The first major step of nucleophilic radiofluorination is drying the aqueous [18F] fluoride which is commonly performed in the presence of a phase-transfer cataylst under azeotropic evaporation conditions (Coenen et al., J. Labelled Compd. Radiopharm., 1986, vol. 23, pgs. 455-467). The [18F] fluoride that is solubilized or dissolved in the target water is often adsorbed on an anion exchange resin and eluted, for example, with a potassium carbonate solution (Schlyer et al., Appl. Radiat. Isot., 1990, vol. 40, pgs. 1-6). One cryptate that is available commercially is 4,7,13,16, 21,24-hexaoxa-1,10-diazabicyclo [8,8,8] hexacosan, with the tradename Kryptofix 222. Cryptate is a cage-like agent that has three ether ribs joining the nitrogens at each end. Alkali metals can be held very strongly inside the cage. Cryptate and other macrocyclic complexing agents are known as the “crown” ethers that consist of large puckered rings held together by several ether linkages.
It has been noted that such a complexing agent should be adsorbed at the site of the electrodes and furthermore, these agents could furnish the electrochemist with a useful cationic adsorbate, with a negative desorption potential. Pospisil et al. has demonstrated that a crown complex of T1+ is adsorbed at a dropping mercury electrode. (Pospisil et al., J. Electroanal. Chem., 1973, vol. 46, pg. 203). Pospisil et al. and Britz et al. demonstrated the use of complex adsorption in the electrosynthesis of tetraethyl lead. (Britz et al., Electrochem. Acta, 1968, vol. 13, pg. 347).
Another useful property of alkali metal ion complexes with cryptates is that the complex is reduced at mercury at much more negative potentials than the uncomplexed ion. This has been examined by Peter and Gross who found a potential shift for the K+ complex of about −1V. (Peter et al., J. Electroanal. Chem., 1974, vol. 53. pg. 307).
In Hamacher et al., an electrochemical recovery of n.c.a. [18F] fluoride in dipolar aprotic solvents and solutions of phase transfer catalyst is discussed. (Hamacher et al., Appl. Radiat. Isot., 2002, vol. 56, pgs. 519-523). This disclosed recovery process allows the use of a specifically designed electrochemical cell as a reaction vessel for n.c.a. nucleophilic [18F]-fluorinations subsequent to [18F] fluoride deposition. In other words, Hamacher et al. uses an electrochemical cell within a chamber that comprises two electrodes across which an electric field is applied. The [18F] fluoride anions are adsorbed onto the surface of the anode while the [18O] water is flushed from the electrode chamber. Hamacher et al. further conclude that a specifically designed electrochemical cell is generally useful for n.c.a. nucleophilic [18F]-radiotracer syntheses. Especially in the case of base labeled products like butyrophenones, the electrochemical cell allows cryptate catalyzed [18F]-fluorination in the presence of weak basic, less nucleophilic salts like potassium oxalate or triflate.
It is important to note here that a cryptand is a phase-transfer agent used to improve the solubility of [18F] fluoride in non-aqueous environments.
Moreover, unlike previous prior art where the adsorption of only cryptands at electrode surfaces have been demonstrated, the present invention presents a method for preparing a robust mono or multi-layers of substituent-substituted cryptands, wherein the mono or multi-layers of electrode-modifying substituent-substituted cryptands can be made via a chemisorption mechanism at open circuit potentials, at the electrode surfaces or via a physisorption mechanism. The cryptate [18F] fluoride complex is then electrochemically desorbed or adsorbed from said surfaces by galvanostatic or by potentiostatic means.
In other words, electrochemical reactions can be driven (and controlled ) at the substiuent-substituted cryptand electrode, in one of the following two formats: one can control the current passing through the cells in a galvanostat or one can control the potential in the cells in a potentiostat.
It is important to note that chemisorption and physisorption used herein are defined as follows:
Chemisorption (or chemical adsorption) is adsorption in which the forces involved are valence forces of the same kind as those operating in the formation of chemical compounds. That is to say, it is the adsorptive process between a molecule and a surface in which the electron density is shared by the adsorbed molecule and the surface.Physisorption (or plysical adsorption) is adsorption in which the forces involved are intermolecular forces (van der Waals forces) and which do not involve a significant change in the electronic orbital patterns of the species involved.
Furthermore, there is a need for creating an electrochemical approach that can increase the yield of [18F] fluoride from the use of electrode materials such as gold, platinum, silver or carbon in which these materials could be tailored to inhibit electrochemical reactions with precursors. It is important to note here that once the fluoride cryptand complex is desorbed from the electrode, the now bare gold electrode, for instance, could be used to promote or inhibit labeling reactions.
Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.